Disposition of intravenous propylthiouracil

Area of Science:

• Pharmacokinetics
• Drug Metabolism
• Renal Physiology

Background:

• Propylthiouracil (PTU) is an antithyroid drug used to treat hyperthyroidism.
• Understanding PTU's pharmacokinetic profile is crucial for optimizing therapeutic efficacy and minimizing adverse effects.

Purpose of the Study:

• To characterize the pharmacokinetic parameters of propylthiouracil following intravenous administration in healthy male volunteers.
• To investigate the extent of renal excretion and identify potential renal tubular reabsorption of PTU.
• To assess the relationship between total and free drug clearance and protein binding.

Main Methods:

• Intravenous administration of propylthiouracil to 10 healthy male volunteers.
• Quantification of plasma and urinary drug concentrations using high-performance liquid chromatography.
• Determination of plasma protein binding via equilibrium dialysis.

Main Results:

• Plasma concentrations of PTU declined biexponentially with a median elimination half-life of 1.28 hours.
• Urinary recovery of unchanged PTU over 24 hours was low (median 1.28%), significantly less than the free fraction in plasma.
• A strong correlation (r=0.95) was observed between total drug clearance and free drug clearance, suggesting predictability.

Conclusions:

• Significant renal tubular reabsorption of propylthiouracil is suggested by the low urinary excretion relative to plasma free fraction.
• Protein binding of PTU in healthy subjects shows modest variation, allowing for prediction of free drug clearance from total clearance.